The objective of this investigation was to study the effect of ethanol upon calcium metabolism in neuronal and non-neuronal membranes. Rat brain synaptosomes and rat erythrocyte ghosts were chosen as model systems. A metallochromic indicator dye, aresnazo III (Az), was employed to detect micromolar changes in cellular Ca. Qualitatively similar results were obtained with synaptosomes (under nondepolarizing conditions) and erythrocyte ghosts. Changes in Ca-Az complex absorbance in the presence of 10-150 mM ethanol in membrane suspensions indicated a release of cellular Ca. Similar effects were observed with theophylline which is already known to stimulate spontaneous release of Ca from intracellular sites in presynaptic terminals. In order to test whether an intracellular release of Ca by ethanol might be involved in our systems, another drug, dantrolene sodium, was employed. The effect of ethanol was diminished when 50 uM dantrolene was present in membrane suspension. These results suggested that ethanol might release Ca from intracellular pools.